Family History Has Complex Role in Alzheimer's Risk

Study Shows ApoE Genes Aren't the Only Factors in the Risk of Alzheimer's Disease

Medically Reviewed by Laura J. Martin, MD on October 10, 2011
From the WebMD Archives

Oct. 10, 2011 -- The role of family history on a person's risk for Alzheimer's disease appears to be more complex than previously recognized, a new study shows.

Scientists once thought that the bulk of genetic risk for late-onset Alzheimer's lay in a set of genes, called ApoE genes, that make a protein that carries cholesterol around the body.

Indeed, several companies have tried to capitalize on the connection between ApoE and Alzheimer's by offering tests that can tell people which version of the ApoE gene they carry.

Now a new study shows that people can still get the kind of brain changes linked to Alzheimer's if they have a family history but don't carry ApoE4, the gene thought to increase Alzheimer's risk.

The study is published in the Archives of Neurology.

"It's a really good study," says Robyn Honea, DPhil, an assistant professor in the Alzheimer's Disease Center at the University of Kansas School of Medicine in Kansas City, Kan. Honea was not involved in the research.

"This is showing that there are other mechanisms at work that are just as related to the disease process as ApoE4," Honea tells WebMD. "And the variety of biomarker tests that they're using in this study really makes that argument because they're really covering the gamut, looking for Alzheimer's-like brains in the most comprehensive way possible."

"This is going along with a lot of other data that myself and others are putting out there that there's a kind of unique genetic mechanism involved outside of this gene," Honea says.

Family History and Biomarkers for Alzheimer's

The study researchers recruited 269 healthy adults who were ages 45 to 75. The participants in the study lived in and around St. Louis.

Most of the volunteers (160) had at least one parent who had developed Alzheimer's before the age of 80. The rest didn't have a parent with Alzheimer's.

People in the study were given a variety of psychological and clinical tests. The psychological tests measured mental abilities like attention and memory. The clinical tests, which included spinal taps and brain scans, measured proteins that are known to accumulate in the brains of people with Alzheimer's disease as well as brain shrinkage. Blood tests were used to look for ApoE genes.

In people who had a family history of Alzheimer's, researchers found significant decreases in levels of beta-amyloid protein in spinal fluid. The lower level of beta-amyloid was true even if people didn't have an ApoE4 gene. There were no significant decreases in people who did not have a family history of the disease.

People in the study who had both a family history and who carried the ApoE4 gene had the largest drops in beta-amyloid in spinal fluid and had the biggest accumulations of beta-amyloid in their brains.

This suggests, experts say, that the presence of the ApoE4 gene is important, but that it doesn't tell the whole story.

Other Genes May Be in Play

Recent large genetic studies have uncovered several other genes that seem to be playing a role in the risk for late-onset Alzheimer's.

"Even though individually these additional non-ApoE risk factors might be quite small, if a family inherited several of them or different combinations of them, then it still can increase one's risk for these changes that relate to Alzheimer's disease independent of any effect of ApoE4," says study researcher John C. Morris, MD. He is a professor of neurology, pathology, immunology, and physical therapy at Washington University in St. Louis.

Morris says some of these genes share the same functions. Several are related to inflammation, for example, and he thinks they may be increasing risk by acting in concert with each other.

Other experts say there could be another explanation, too.

"Family history is not completely just genetics," says Brian Appleby, MD, a staff physician at the Lou Ruvo Center for Brain Health at Cleveland Clinic, Ohio. He was not involved in the research.

Appleby points out that families also tend to eat the same kinds of foods and share patterns of physical activity. And lifestyle is also thought to play a powerful role in Alzheimer's disease risk.

"It could be the way someone was raised and environmental factors and lifestyle factors. I think those things have to be considered, too."

Show Sources


Xiong, C. Archives of Neurology, Oct. 10, 2011.

John C. Morris, MD, professor of neurology, pathology, immunology, and physical therapy, Washington University, St. Louis.

Robyn Honea, DPhil, assistant professor, Alzheimer's Disease Center, University of Kansas School of Medicine, Kansas City, Kan.

Brian Appleby, MD, staff physician, Lou Ruvo Center for Brain Health, Cleveland Clinic, Ohio.

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